Initial Human PET Studies of Metabotropic Glutamate Receptor Type 1 Ligand 11C-ITMM

N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-11C-methoxy-N-methylbenzamide (11C-ITMM) is a potential radioligand for mapping metabotropic glutamate receptor type 1 (mGluR1) in the brain by PET. The present study was performed to determine the safety, distribution, radiation dosimetry, and initial brain imaging of 11C-ITMM in healthy human subjects. Methods: The multiorgan biodistribution and radiation dosimetry of 11C-ITMM were assessed in 3 healthy human subjects, who underwent 2-h whole-body PET scans. Radiation dosimetry was estimated from the normalized number of disintegrations of source organs using the OLINDA/EXM program. Five healthy human subjects underwent 90-min dynamic 11C-ITMM scans of brain regions with arterial blood sampling. For anatomic coregistration, T1-weighted MR imaging was performed. Metabolites in plasma and urine samples were analyzed by high-performance liquid chromatography. 11C-ITMM uptake was assessed quantitatively using a 2-tissue-compartment model. Results: There were no serious adverse events in any of the subjects throughout the study period. 11C-ITMM PET demonstrated high uptake in the urinary bladder and gallbladder, indicating both urinary and fecal excretion of radioactivity. The absorbed dose (μGy/MBq) was highest in the urinary bladder wall (13.2 ± 3.5), small intestine (9.8 ± 1.7), and liver (9.1 ± 2.0). The estimated effective dose for 11C-ITMM was 4.6 ± 0.3 μSv/MBq. 11C-ITMM showed a gradual increase of radioactivity in the cerebellar cortex. The total distribution volume in the brain regions ranged from 2.61 ± 0.30 (cerebellar cortex) to 0.52 ± 0.17 (pons), and the rank order of the corresponding total distribution volume of 11C-ITMM was cerebellar cortex > thalamus > frontal cortex > striatum ≈ pons, which was consistent with the known distribution of mGluR1 in the primate brain. The rate of 11C-ITMM metabolism in plasma was moderate: at 60 min after injection, 62.2% ± 8.2% of the radioactivity in plasma was intact parent compound. Conclusion: The initial findings of the present study indicated that 11C-ITMM PET is feasible for imaging of mGluR1 in the brain. The low effective dose will permit serial examinations in the same subjects.